Sickle cell disease (hereinafter “SCD”) is a genetic hematological disorder characterized by sickle-shaped red blood cells. SCD may result in arthralgia (joint pain), acute attacks of abdominal pain, pain in the hands and feet (“hand-foot syndrome”), long bone pain, ulceration of lower extremities, anemia, infections, and stroke. The symptoms of SCD may begin in childhood, sometimes as early as 6 months of age. SCD causes anemia. SCD may also lead to or be associated with other conditions such as vaso-occlusive crisis; splenic sequestration crisis; acute chest syndrome; aplastic crisis; or haemolytic crisis. Vaso-occlusive crisis is caused by the sickle-shaped red blood cells restricting or obstructing flow of blood to an organ and may produce pain and organ damage. Splenic sequestration crisis is the painful enlargement of the spleen caused by the trapping of red blood cells in the narrow vessels of the spleen.
The pain associated with the various manifestations of SCD has been treated with common over-the-counter pain medications such as aspirin, acetaminophen, and other nonsteroidal anti-inflammatory agents (NSAIDs) such as ibuprofen, naproxen or diclofenac. In cases of more severe pain, opioids may be administered either orally or intravenously. Continued or prolonged administration of analgesics such as aspirin, acetaminophen, and NSAIDs may lead to gastrointestinal bleeding or ulcers, and some NSAIDs may lead to heart failure and stroke. Opioids are a class of drugs known to have strong analgesic effects in humans, however, opioids have numerous undesirable side effects such as itchiness, sedation, nausea, respiratory depression, constipation, and euphoria. Furthermore, continuous opioid use can lead to dependence often resulting in withdrawal syndrome. Moreover, because of the euphoric effects of opioids, recreational use is common and may lead to accidental overdose and death from respiratory depression. Currently, the United States is experiencing an increase in the rates of recreational use of opioids and addiction, which many attribute to the over-prescription of opioids for pain management.
Accordingly, there is a need for improved pain treatments for patients suffering from SCD that produces fewer side effects, does not produce respiratory depression, and has less abuse potential than opioids. Similarly, there is also a need for effective treatments of pain experienced by patients with SCD that allows for reduced doses of opioids and/or NSAIDs to thereby reduce the incidences of side effects and dependency.